Uncontrolled cell division is a hallmark of cancer. Although much progress has been made in deciphering the molecular basis of tumorigenesis, a deeper understanding of the complexities of cell cycle progression will be necessary for the development of novel therapeutic strategies. The transition from G2 to M phase is a highly regulated step in the cell division cycle, and as such, some proteins involved in this process are targeted in human cancers. Thus, basic research on the mechanism of mitotic entry is an important part of cancer research. The goals of this research are: 1) to define the contribution of Cdkl/cyclin B towards mitotic entry, and 2) to identify and characterize novel substrates of Cdkl/cyclin B that drive the transition from G2 phase to M phase of the vertebrate cell cycle. A chemical-genetic screen will be used to identify a comprehensive set of protein substrates for the Cdkl/cyclin B complex. Substrates will be characterized for their roles in cell cycle progression using a combination of cell biological and biochemical methods. Results from these studies will contribute toward a more detailed understanding of the events of early mitosis, including how the rise of Cdkl/cyclin B activity during late G2 phase ultimately drives entry into mitosis.